Radiography, especially X-ray radiography, has long been used widely as a medical technique for diagnosis and analysis of various diseases. However, not a few parts of the body such as the vasculature, the urinary tract, the gallbladder, the bile duct and the cerebrospinal cavity require a contrast medium for a higher resolution. In particular, angiography is almost indispensable to diagnosis of various angiopathies, mainly in the tissues of extremities and the brain, and medical need for angiography is increasing. As contrast media for angiography, 2,4,6-triiodobenzoic acid derivative type compounds represented by iopamidol, iohexol and ioxaglate are now in use. However, contrast media with a higher contrasting ability are required for diagnosis in an increasing number of cases. In addition, at present, the side effects of these media for injection, such as heat and pain at the time of injection due to their osmotic pressures higher than that of the blood, and nausea, vomiting and eruption, which are thought as peculiar to iodine compounds, are regarded as questionable.
As a method of improving contrasting ability, compounds having more iodine atoms introduced per molecule are conceivable, however, they seem to have many problems in practical use due to their chemical instability and difficulties in their production. On the other hand, some compounds containing atoms with nuclei larger than that of an iodine atom, are theoretically thought to exhibit a higher contrasting ability commensurate with their radiation shielding power. However, the enhanced chemical instability accompanied by enlargement of atomic nuclei, difficulties in their production and the toxicity are seriously problematic in practical use of these compounds as a contrast medium.
Bismuth is an element of atomic number 83 which belongs in the periodic table to group V and period 6, and is known to have a larger atomic nucleus than iodine does. In general, organic bismuth compounds, typically trialkylbismuths, are poor in chemical stability, but some triphenylbismuths are reported to be comparatively stable.
The good point of triphenylbismuths is that they are expected to have higher contrasting ability at short wavelengths around 0.1 .ANG.. This is supported by the fact that bismuth has a larger mass absorption coefficient (0.345) at 0.1 .ANG. than iodine (0.136) and thus has a high X-ray shielding ability.
Considering that present diagnostic X-ray examinations are conducted with long wavelengths which are harmful to the body, this means that use of triphenylbismuths is as radiographic contrast media brings a great advantage in terms of safety and resolution.
The relations between the organic bismuth derivatives of general formula (I) and their salts of the present invention and analogous compounds disclosed in prior art documents are discussed below.
(a) Vestn. Lenigrad. Univ., Fiz., Khim., 4, pp113-116, 1971; Chemical Abstracts, vol. 76 (20), 119603, discloses tris(p-substituted phenyl)bismuth compounds having a sulfonamide group (NH.sub.2 SO.sub.2 --) or a methoxy group at the p-position of each benzene ring.
(b) Phosphorus Sulfur., vol. 14 (2), pp253-260, 1983 discloses tris(2,6-dialkoxyphenyl)bismuth compounds which have a methoxy group or an ethoxy group at each of the 2 and 6-positions of each benzene ring.
(c) J. Coord. Chem., vol. 12, pp53-57, 1982 discloses tris(o-substituted phenyl)bismuth compounds having a methoxy group, a methylthio group or a dimethylamino group at the o-position of each benzene ring.
None of the above documents (a)-(c) disclose any use of those bismuth compounds, much less medical use of them.